A number of patent and non-patent documents have proposed the results of many studies on the carrier to deliver growth factors.
For example, Korean Patent Application No. 10-2008-0100315 discloses a preparation method for porous calcium phosphate granules and a manufacturing method for a functional bone graft material using the same.
However, this technology involves loading growth factors in a simple manner of adsorption, but without using a material to bind the bone morphogenetic proteins to the support, so the bone morphogenetic proteins are released in a short period of time (fast release) with the difficulty in controlling the release rate, more likely causing an adverse effect that the tissue grows excessively faster than usual in the course of tissue regeneration [Yeh, T. T., S. S Wu et al., Osteoarthritis Cartilage 15(12): 1357-1366, 2007]. In addition, the technology adopts adsorption and freeze-drying of proteins, thus more possibly ends up transforming the structure of the bone morphogenetic proteins and has the difficulty in sterilizing the bone graft material on which the bone morphogenetic proteins are adsorbed.
The carrier for growth factor is a pharmaceutical preparation injected into the human body and hence subjected to proven sterilization methods, such as gamma radiation sterilization, E-beam sterilization, or high-pressure steam sterilization, ethylene oxide (E.O.) gas sterilization, in the manufacturing process of medical equipment. These sterilization methods involve irradiation of heat or radioactive rays to have an effect on the structure of the proteins. Therefore, the bone morphogenetic proteins after the sterilization process not only fail to achieve their intended effects sufficiently but also become recognized as transformed proteins in the human body, with high possibility of causing an adverse effect [Chen, J. B. et. Al., J Biomed Mater Res A, 80(2): 435-443, 2007].
On the other hand, International Patent Application No. PCT/EP2008/005340 discloses the technology related to a composite bone repair material including a porous block type ceramic scaffold and a stabilizing polymer arranged in the support.
The ceramic scaffold is immersed in an aqueous solution of polyethylene glycol thio (PEG-thiol)containing bioactive substances, such as parathyroid hormone (PTH), bone morphogenetic protein (BMP), enamel matrix derivative (EMD), etc., and a polymer mixture of polyarm polyethylene glycol acrylate (polyarm PEG-acrylate) to form a bone repair material that contains bioactive substances. But, the polymers used in this method, that is, the aqueous solution of PEG-thiol and polyarm PEG-acrylate are free from the portion to bind the bioactive substances to the support, so it is impossible to achieve a controlled release of the growth factors as specified above. The results of the PTH release test proposed in this document show that the release of the growth factors is completed in 5.8 days. When such a release profile is applied to the bone morphogenetic proteins (BMPs) that are growth factors for bone generation and organization, the bone morphogenetic proteins (BMPs) can be released excessively fast (fast release) to cause an adverse effect on the bone generation or bone regeneration, such as generating bone in the regions other than the bone tissue or failing to achieve a fast regeneration of bone in the damaged bone tissue.
Further, International Patent Application No. PCT/IB2009/005235 discloses a bone morphogenetic composition prepared by mixing a bone morphogenetic growth factor/amphipathic anionic polysaccharide composite and at least one at least divalent cationic soluble salt and processed into an open implant in the freeze-dried form. This document suggests the use of hyaluronic acid to promote the effect of the growth factors, but no approach to the method for controlling the delivery rate of the growth factors.
In addition, Korean Patent Application No 10-2008-0038777 specifies a hyaluronic acid bone void filler composite and a preparation method thereof, which the hyaluronic acid bone void filler composite is prepared by adding a calcium phosphate derivative to a matrix including hyaluronic acid to induce bone regeneration by the osteoconductive action of the hyaluronic acid.
However, the technology disclosed in the document relates to the bone void filler used to fill in the bony voids but does not suggest any technology regarding the carrier for growth factor promoting bone generation. Moreover, the calcium phosphate compound used as a bone regeneration inducer composed of hydroxyapatite and β-TCP is prepared by the chemical precipitation reaction, and it is thus impossible to control the porosity of the bone void filler. Further, the porosity of the bone void filler cannot be controlled when the calcium phosphate compound is used as a carrier for growth factor. As the pores are not interconnected with one another, neither the growth factor can be loaded in the bone void filler nor the release rate of the growth factor can be under control. Furthermore, there possibly occurs a fast release of the growth factors. As a result, the bone void filler is not suitable as a carrier for growth factor.
In other words, as the most important thing is that the carrier for growth factor for regeneration of bone tissues can be injected into the human body, the carrier for growth factor is required to be sterilized with little toxicity. In addition, the carrier for growth factor has to be biodegradable and capable of controlling the delivery rate of the growth factors arbitrarily as suitable to the size or degree of the bone voids and reducing the adverse effect possibly caused in the case of the fast release of the growth factors. Most of all, an efficient regeneration of the bone tissues takes place when the growth factors are released suitably according to the regeneration rate of the damaged tissue and only on a confined region of the damaged tissue. However, the above-specified conventional technologies do not suggest any solution to the above-mentioned problems with the carrier for growth factor for regeneration of bone tissues and there is still a need for the carrier for growth factor for regeneration of bone tissues to solve the problems.